The research program is directed towards studying the biochemistry and physiology of the nerve terminal with particular emphasis on intracellular ion transients, modulation of secretion and mechanism of exocytotic secretion. The neurohypophysial nerve terminals are used as the model to study the importance of ion channels and receptors on initiation and modulation of secretion. These include studies on secretion of vasopressin and oxytocin from isolated neurosecretosomes, and calcium ion transients in the nerve terminals. Neurosecretosomes are maintained under tissue culture conditions and this preparation is suitable for studies of the mechanism of secretion, and high resolution microscopy. Neurosecretosomes respond to depolarizing stimuli with markedly elevated secretion. Calcium ionophores also cause secretion in the absence of applied depolarization. The inactivation of hormone release from neurosecretosomes was found to be independent of membrane depolarization. Tetanus toxin in nM concentrations blocks secretion of both hormones induced by depolarizing stimuli, as well as by calcium ionophores. Secretion of both hormones was inhibited by the opiate k-receptor agonists and somatostatin. This receptor-mediated modulation of secretion at the nerve terminal is under investigation. Analogues of FMRFamide related peptides have been developed to study their receptors in mammalian and squid CNS. A study of synaptic vesicle associated proteins in the squid resulted in the characterization of low molecular weight GTP-binding proteins and synaptobrevin. A cell-free system and a permeabilized cell model are being developed to study the exocytotic process.